1. Field of the Invention
The present invention generally relates to a pharmacophore for antimalarial activity. In particular, the present invention relates to a pharmacophore derived from tryptanthrin compounds and how to increase the solubility and bioavailability of the compounds.
2. Description of the Related Art
The current global situation with respect to malaria indicates that about two billion people are exposed to the disease and of these 400 million people are already infected. See Trigg, P. I., and A. V. Kondrachine (1998) The Current Global Malaria Situation, Chapter 2, p. 11-22, in MALARIA PARASITE BIOLOGY, PATHOGENESIS AND PROTECTION. Ed. I. W. Sherman, ASM Press, Washington, D.C. Each year between 100 to 200 million new cases of infection are reported and approximately 1 to 2 million people die due to malaria. The situation is rapidly worsening mainly due to non-availability of effective drugs and development of drug resistance of a large number of non-immune people in areas where malaria is frequently transmitted. See White, N. J. (1998) Br. Med. Bull. 54:703-715.
In an increasingly wide geographic area, both Plasmodium falciparum and Plasmodium vivax have been developing resistance to chloroquine, the most successful antimalarial drug in the past several decades. Mefloquine and doxycycline, the two other frontline drugs for the treatment and prevention of malaria are becoming increasingly ineffective. See Vroman, J. A. et al. (1999) Curr. Pharm. Design 5:101-138. Artemisinin analogs such as artesunate and arteether were later introduced that are found to be quite effective, particularly against drug-resistant P. falciparum but observations of drug-induced and dose-related neurotoxicity in animals have raised concern about the safety of these compounds for human use. See Bhattacharjee, A. K. and J. M. Karle (1999) Chem. Res. Toxicol. 12: 422-428. Therefore, much effort and attention are needed for the discovery and development of new and less toxic antimalarial drugs.